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目的探讨细胞色素C对依替米星在大鼠肾脏中的蓄积及其致肾小管毒性的影响。方法将48只SPF级雄性Wistar大鼠按随机数字表分为8组,即溶媒对照组、细胞色素C组、依替米星10 mg/kg组、依替米星10 mg/kg+细胞色素C组、依替米星30 mg/kg组、依替米星30 mg/kg+细胞色素C组、依替米星100 mg/kg组和依替米星100 mg/kg+细胞色素C组,每组6只。溶媒对照组腹腔注射生理盐水;细胞色素C组腹腔注射细胞色素C 100 mg/(kg.d);单用依替米星各组分别腹腔注射依替米星10、30、100 mg/(kg.d);依替米星加用细胞色素C的3组先尾静脉注射细胞色素C 100 mg/(kg.d),约30 min后再分别腹腔注射依替米星10、30、100 mg/(kg.d)。每组大鼠均连续给药3 d,最后一次给药后24 h处死大鼠,摘取双侧肾脏,高效液相色谱法测定肾组织中依替米星蓄积量,脱氧核苷酸末端转移酶介导的缺口末端原位标记法检测肾小管上皮细胞凋亡情况,用CMIAS-Ⅱ医学图像分析系统计算凋亡阳性细胞数密度。结果大鼠肾组织中依替米星浓度如下:依替米星10、30和100 mg/kg组,其浓度分别为(69.3±16.9)、(221.8±66.8)和(305.9±35.5)μg/g;依替米星加细胞色素C组,其浓度分别为(39.0±18.4)(P<0.05)、(121.5±34.2)(P<0.05)和(266.7±43.7)μg/g。大鼠肾小管上皮凋亡细胞数密度如下:依替米星10、30和100 mg/kg组,其密度分别为(266.8±15.4)、(527.7±208.7)和(528.8±145.3)个/mm2;依替米星加细胞色素C组,其密度分别为(97.2±15.4)(P<0.01)、(162.4±36.6)(P<0.01)和(472.5±70.1)个/mm2。结论细胞色素C可抑制依替米星在肾组织中的蓄积进而抑制其所致肾小管毒性。
Objective To investigate the effect of cytochrome C on the accumulation of etimicin in rat kidneys and its renal tubular toxicity. Methods Forty-eight SPF male Wistar rats were randomly divided into 8 groups: vehicle control group, cytochrome C group, etimicin 10 mg / kg group, etimicin 10 mg / kg + cytochrome C Group, etimicin 30 mg / kg group, etimicin 30 mg / kg + cytochrome C group, etimicin 100 mg / kg group and etimicin 100 mg / kg + cytochrome C group, and each group 6 only. The control group was injected intraperitoneally with normal saline. Cytochrome C group was injected intraperitoneally with Cytochrome C 100 mg / (kg · d). Etimicin alone was injected intraperitoneally with 10, 30 and 100 mg / kg . Etirmicin plus Cytochrome C in the three groups of tail vein injection of cytochrome C 100 mg / (kg.d), about 30 min and then were injected intraperitoneally etimicin 10,30,100 mg / (kg.d). Rats in each group were given continuous administration for 3 days and rats were sacrificed 24 hours after the last administration. Both kidneys were harvested and the amount of etimicin accumulation in renal tissues was determined by high performance liquid chromatography. The terminal deoxynucleotidyl transferase Enzyme-mediated nick end labeling in situ was used to detect the apoptosis of renal tubular epithelial cells. The number of apoptotic positive cells was calculated by CMIAS-II medical image analysis system. Results The concentration of etimicin in rat renal tissue was as follows: etimicin at concentrations of 30, 30 and 100 mg / kg were (69.3 ± 16.9), (221.8 ± 66.8) and (305.9 ± 35.5) μg / g and etimicin plus cytochrome C group were 39.0 ± 18.4 (P <0.05), (121.5 ± 34.2) (P <0.05) and (266.7 ± 43.7) μg / g, respectively. The number of apoptotic cells in renal tubular epithelial cells of rats was as follows: The eustachymidine groups were (266.8 ± 15.4), (527.7 ± 208.7) and (528.8 ± 145.3) / mm2 respectively at the 10, 30 and 100 mg / (97.2 ± 15.4) (P <0.01), (162.4 ± 36.6) (P <0.01) and (472.5 ± 70.1) / mm2, respectively. Conclusion Cytochrome C can inhibit the accumulation of etimicin in renal tissue and thus inhibit the renal tubular toxicity.